Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Sachs 6th Annual Neuroscience Innovation Forum and JP Morgan Healthcare Conference week 20 (January 2023)
30 slides from Actinogen Medical's conference presentation, Jan 9, 2023
Slide 1: ASX Announcement: CEO presents at Sachs Neuroscience Forum and JPM week
For personal use only ASX ANNOUNCEMENT Actinogen CEO presents latest clinical data at Sachs Annual Neuroscience Innovation Forum and other meetings during the JP Morgan Healthcare Conference week Sydney, 08 January 2023. Actinogen Medical Ltd ASX: ACW (“ACW” or “the Company”) announces that CEO Dr S
Slide 2: About Actinogen Medical and Xanamem
ENDS Investors Dr. Steven Gourlay Michael Roberts CEO & Managing Director Investor Relations P: +61 2 8964 7401 M: +61 423 866 231 For personal use only E. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au Announcement authorised by the Board of Directors of Actinogen Medical About
Slide 3: For personal use only
economic and competitive uncertainties / contingencies and regulatory and clinical development risks, future outcomes and uncertainties) that may lead to actual results being materially different from any forward looking statement or the performance expressed or implied by such forward looking state
Slide 4: Third trial validates Xanamem cognitive activity & Alzheimer's Disease program
For personal use only Third trial validates Xanamem® cognitive activity & Alzheimer’s Disease program Positive Phase 2a data with large CDR-SB effect size Dr. Steven Gourlay MBBS PhD MBA, CEO & MD Sachs 6th Annual Neuroscience Forum and JP Morgan Healthcare Conference week, 8-12 January 2023 Authori
Slide 5: Disclaimer
Disclaimer For personal use only This presentation has been prepared by Actinogen Medical Limited. (“Actinogen” or the “Company”) based on information available to it as at the date of this presentation. The information in this presentation is provided in summary form and does not contain all inform
Slide 6: Xanamem: Oral, low dose, once-a-day treatment with a unique mechanism
Xanamem: Oral, low dose, once-a-day treatment For personal use only with a unique non-amyloid/tau mechanism Brain penetrant 11β-HSD1 small molecule enzyme inhibitor reduces cortisol inside brain cells - modulating signaling pathways and underlying disease processes1,2 Potential to be: • Rapidly cogn
Slide 7: PET data shows full target engagement in the brain at 5-10 mg
PET data shows full target engagement in the brain at well tolerated doses of 5-10 mg For personal use only Previous molecules to this target have not achieved adequate brain concentrations Baseline After Dose PET data demonstrates that Xanamem extensively binds to the 11β-HSD1 enzyme 5 mg Xanamem 1
Slide 8: Xanamem Phase & program
Xanamem Phase 2 & 3 program Building on four independent Phase 1 and 2 studies showing activity For personal use only Current Phase 1 & 2a, biomarker Safety, cognition activity (n~300) Phase 2b Phase 2a Cognitive Impairment Alzheimer’s Disease (AD) in Depressive Disorder (CIDD) Phase 3 Phase 3 Alzhe
Slide 9: Previously: evidence of Xanamem activity on cognition from multiple sources
Previously: evidence of Xanamem activity on cognition from multiple sources For personal use only ✓ In animals ✓ Protection against cognitive decline in animal model of AD using a Xanamem analogue independent of amyloid plaque1 ✓ In humans ✓ Consistent target engagement measured by PET & ACTH respon
Slide 10: Phase 2a blood biomarker study design & methods
Phase 2 blood biomarker study design & methods Uses a pre-specified protocol and analysis plan to avoid bias For personal use only Assess efficacy trends on Measure disease clinical endpoints biomarkers Week 0 & 12 • Prespecified analysis to avoid bias 72 patients with • pTau181 • Select by baseline
Slide 11: Clinical Dementia Rating – Sum of Boxes (CDR-SB)
Clinical Dementia Rating – Sum of Boxes (CDR-SB) functional endpoint to assess dementia in early-stage AD For personal use only Test domain Impairment None Questionable Mild Moderate Severe 0 0.5 1 2 3 Memory Orientation Judgment & Problem Solving Community Affairs Home & Hobbies Personal Care Score
Slide 12: Xanamem doubled rate of disease stabilization on CDR-SB endpoint
Xanamem doubled rate of disease stabilization on FDA-approved CDR-SB endpoint For personal use only Response analysis in pTau-positive1 AD patients (most likely to progress) Twice as many patients in the Xanamem group had stable or improved disease compared with placebo2 … meaning 56% of patients tr
Slide 13: Topline result from pre-specified analysis in AD patients with high pTau181
Topline result from pre-specified analysis in AD patients with plasma pTau181 > median of 6.74 pg/mL For personal use only Using pre-specified protocol, statistical analysis plan and blinded biomarker analysis Xanamem Placebo -1 -0.5 CDR-SB units Change from 0 0 0 Baseline (SE) 0.5 0.36 * * Differen
Slide 14: Effect on CDR-SB in other three pre-specified groups
Effect on CDR-SB in other three pre-specified groups Groups defined by biomarker median value, MMSE by 20-23 vs. 24-26 For personal use only N CDR-SB Group Desired Xanamem Placebo Cohen’s p value change d pTau >10.2 pg/mL1 (mean) 9 Down 0.1 0.8 0.6 0.33 Aβ42/40 ratio < 0.19 (mean) 29 Down 0.5 0.4 0.
Slide 15: Exploring the high pTau group: baseline characteristics
Exploring the high pTau group: baseline characteristics For personal use only Xanamem Placebo (n=16) (n=18) Age (mean, SD) 71 (8) 71 (8) % female 50% 56% % donepezil therapy1 44% 61% ADASCog14 (mean, SD) 34 (5) 32 (8) ADCOMS (mean, SD) 0.56 (0.13) 0.52 (0.19) MMSE (mean, SD) 22 (3) 23 (2) CDR-SB (me
Slide 16: High pTau group: NTB and other endpoints
High pTau group: NTB and other endpoints For personal use only NTB: a composite for executive function consisting of Controlled Oral Word Association (COWAT) and Category Fluency Test (CFT) • Improved NTB: Xanamem +0.5 vs. Placebo -2.3, Cohen’s d = 0.3 • No effects on ADAS-Cog14, ADCOMS, MMSE, RAVLT
Slide 17: Exploratory: Change from baseline in cognitive composite
Exploratory: Change from baseline in cognitive composite For personal use only Trends in change of composite of word recall & recognition, CFT & COWAT (p=NS) Higher pTau181 Lower pTau181 0.3 0.3 Composite Units (SE*) Composite Units (SE) 0.2 0.2 0.1 0.1 0 0 -0.1 -0.1 -0.2 -0.2 -0.3 -0.3 Worse Xaname
Slide 18: Exploratory: Change from baseline in cognitive-functional composite
Exploratory: Change from baseline in cognitive-functional composite (with CDR-SB) For personal use only Trends in change of composite of CDR-SB, word recall & recognition, CFT, COWAT Higher pTau181 Lower pTau181 0.2 0.2 0.1 0.1 Composite Units (SE*) Composite Units (SE) 0 0 -0.1 -0.1 -0.2 -0.2 -0.3
Slide 19: The new analysis validates and de-risks the AD program
The new analysis validates and de-risks the AD program For personal use only ✓ Confirming clinical activity of Xanamem in mild AD patients ✓ Large clinical effect size ✓ Utility of blood pTau levels to select suitable patients for next Phase 2b trial ✓ Utility of CDR-SB to measure the benefit of Xan
Slide 20: Moving forward rapidly in Cognitive Impairment in AD and Depression
For personal use only Moving forward rapidly in Cognitive Impairment in AD and Depression Biomarker data validate planned Phase 2b protocol in Mild Cognitive Impairment / mild AD with positive blood pTau CEO presentation JP Morgan Healthcare Week 2023 17
Slide 21: Focus on speed to approval with 6 and 9-month trials
Focus on speed to approval with 6 and 9-month trials For personal use only No functional impairment XanaMIA Functional impairment & loss of independence XanaMIA Phase 1b Phase 2b Healthy 50-80 MCI/early AD1 patients years Mild • N=330, placebo-controlled • pTau patient selection • 10 mg vs. placebo
Slide 22: XanaMIA Phase 2b trial design & implementation model
XanaMIA Phase 2b trial design & implementation model: selecting AD patients by blood pTau level For personal use only 10mg Xanamem Screening 5mg Xanamem Follow-up & open label Placebo -4 0 24 28 Weeks Double-blind, randomised treatment period (N=330) Key inclusion/exclusion criteria Primary Endpoint
Slide 23: Science Behind the Xanamem Depression Program
Science Behind the Xanamem Depression Program For personal use only ✓ 80-90% report neurocognitive symptoms1 ✓ Cognitive symptoms often persist during remission1 ✓ Elevated cortisol associated with severe, melancholic depression2 ✓ Cortisol levels associated with treatment outcomes, relapse, & cogni
Slide 24: XanaCIDD trial design & implementation model
XanaCIDD trial design & implementation model For personal use only 10mg Xanamem Follow-up Screening Placebo -4 0 6 10 Weeks Double-blind, randomised treatment period (N=160) Key inclusion/exclusion criteria Primary Endpoints Key Secondary Endpoints Key Implementation Features • Primary diagnosis of
Slide 25: Xanamem Development: Strategy & Timelines
For personal use only Xanamem Development: Strategy & Timelines CEO presentation JP Morgan Healthcare Week 2023 22
Slide 26: Actinogen strategy validated by new trial results
Actinogen strategy validated by new trial results Backed by strong balance sheet and intellectual property For personal use only Accelerate clinical development Create value from partnerships • Focus on cognitive enhancement: Pharma/biotech engagement • Patients with early Alzheimer’s Disease • Acti
Slide 27: Two major Phase 2 trials of Xanamem in 2023-24
Two major phase 2 trials of Xanamem in 2023-24 For personal use only • Two positive, independent clinical trials • Commercial tablet manufacturing 2022 • XanaCIDD trial started enrolling in Depression • FDA “clear to proceed” with Phase 2b in AD • XanaMIA Phase 2b enrollment starts H1 • XanaMIA Phas
Slide 28: Appendix
For personal use only Appendix CEO presentation JP Morgan Healthcare Week 2023 25
Slide 29: Selected glossary
Selected glossary 1 For personal use only 11β-HSD1 11 beta HydroxySteroid Dehydrogenase-1 enzyme Aβ Amyloid beta – a type of amyloid protein associated with Alzheimer’s Disease, 42 and 40 are different forms ACTH Adrenocorticotropic hormone that regulates blood levels of cortisol ADAS-Cog Alzheimer’
Slide 30: Selected glossary
Selected glossary 2 For personal use only IQCODE Informant Questionnaire on Cognitive Decline in the Elderly MCI Mild Cognitive Impairment – memory, executive function deterioration with retained functional abilities MDD Major Depressive Disorder MMSE Mini Mental State Examination – a 30-point scale